Three lines of research are being pursued: 1) Sugar permeability of plasma membrane of barnacle giant muscle fiber: It has perviously been found that decreses in intracellular ATP and cyclic nucleotides resulted in decreases in the rate constant for efflux of injected radioactive 3-0-methylglucose (3-0-MG). Continuation of these experiments showed that a decrease in rate constant can also be produced by decreasing intracellular pH by injection of an appropriate buffer. The effects of membrane potential, internal ATP, cyclic nucleotides, pH, and ionized calcium will be determined in muscle fiber subjected to continuous internal and external perfusion. 2) Effort to produce in vivo insulin effects with phosphatidyl inositol (PI) liposomes: Research in other laboratories has shown that in vitro exposure of cells to liposomes consisting of PI produces insulin-like effects. Experiments were carried out in which fasted mice were injected with PI liposomes in an attempt to produce insulin shock. As yet, no evidence of insulin shock has been obtained even though sufficient PI was injected to result in plasma and interstitial fluid levels of PI which were up to 10 to 20 times the levels effective in vitro. 3) Autoradiography of muscle fibers: In an attempt to obtain direct evidence on whether or not the lumen of the sarcoplasmic retitculum (SR) of skeletal muscle fibers is continuous with the external fluid compartment, muscle fibers have been exposed to solutions containing either tritiated inulin (which is thought to be excluded from the SR) or tritiated sucrose (which may or may not be free to enter the SR). If sucrose cannot enter the SR, inulin and sucrose autoradiograms should be similar. If sucrose can enter the SR, the autoradiograms should be different.